Interleukin 1- and tumor necrosis factor-stimulation of prostaglandin E2 synthesis in MDCK cells, and potentiation of this effect by cycloheximide.
The effects of interleukin (IL)-1 alpha, IL-1 beta and TNF alpha on prostaglandin-E2 synthesis in Madin-Darby canine kidney (MDCK) cells were investigated. IL-1 beta time- and dose-dependently stimulated prostaglandin-E2 synthesis. While TNF alpha produced a comparatively small but significant stimulation of PGE2 release, coincubation of IL-1 beta with TNF alpha produced a marked synergistic stimulation of PGE2 release. The effect of IL-1 beta and of IL-1 beta and TNF alpha was apparent as early as after 2 h of incubation. The enhanced PGE2 synthesis was inhibited by indomethacin as well as actinomycin D, while cycloheximide surprisingly potentiated PGE2 synthesis in response to both IL-1 beta and TNF alpha. IL-1 alpha alone was ineffective in stimulating a significant release of PGE2 at concentrations as high as 10 nM. However, it also showed a marked synergistic interaction with TNF alpha in stimulating PGE2 release.
Leighton
J D
JD
Research Department, Ciba-Geigy AG, Basel, Switzerland.
Pfeilschifter
J
J
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis*; D004285:Dogs; D004357:Drug Synergism; D007375:Interleukin-1 / Q000494:pharmacology*; D007668:Kidney; D007700:Kinetics; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D007375:Interleukin-1; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D003513:Cycloheximide; D015232:Dinoprostone